How a few drops of blood led to a breakthrough in immunology

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MUHC researchers pinpoint the roles of FOXP3 – a key gene in the regulation of our immune system

Scientists from the Research Institute of the McGill University Health Centre (RI-MUHC) may have cracked the code to understanding the function of special cells called regulatory T Cells. Treg cells, as they are often known, control and regulate our immune system to prevent excessive reactions. The findings, published in Science Immunology, could have a major impact in our understanding and treatment of all autoimmune diseases and most chronic inflammatory diseases such as arthritis, Crohn’s disease as well as broader conditions such as asthma, allergies and cancer. 

Researchers made this discovery by investigating a rare human mutation in a gene called FOXP3. Although the importance of the FOXP3 gene in the proper function of Treg cells has been well documented, its mechanisms were still not fully understood by scientists. 

“We discovered that this mutation in the FOXP3 gene affects the Treg cell’s ability to dampen the immune response, which results in the immune system overreacting and causing inflammation,” explains the study’s lead author, Dr. Ciriaco Piccirillo, immunologist and senior scientist in the Infectious Diseases and Immunity in the Global Health Program at the RI-MUHC, and a professor of Immunology at McGill University. “This discovery gives us key insights on how Treg cells are born and how they can be regulated.” 

Thanks to an international collaboration and cutting-edge technology from the Immunophenotyping Platform at the RI-MUHC, the team was able to make their discovery using only a few drops of blood from a five-week-old newborn boy who died in 2009 from a rare and often fatal inherited genetic immune disorder called IPEX. In the past 40 years, fewer than 200 cases of IPEX have been identified worldwide. Over 60 different mutations of the FOXP3 gene are known to cause IPEX and believed to result in non-functional Treg Cells. 

“What was unique about this case of IPEX was that the patient’s Treg cells were fully functional apart from one crucial element: its ability to shut down the inflammatory response,” says Dr. Piccirillo. 

“Understanding this specific mutation has allowed us to shed light on how many milder forms of chronic inflammatory diseases or autoimmune diseases could be linked to alterations in FOXP3 functions,” adds the study’s first author, Khalid Bin Dhuban, a postdoctoral fellow in Dr. Piccirillo’s laboratory.

Read more about it on MUHC.CA